Impact of tumor subsite on survival outcomes in oral squamous cell carcinoma: A retrospective cohort study from 2000 to 2019.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is responsible for high morbidity and mortality worldwide. Although the oral cavity encompasses different anatomical subsites, it is unclear whether subsite localization of carcinoma influences outcome. METHODS: This retrospective cohort study examined overall survival (OS), recurrence-free survival (RFS) and local recurrence-free survival (L-RFS) at different subsites by Kaplan-Meier survival curves. Cox proportional hazards regression analysis was performed to investigate the impact of subsite on overall death, locoregional recurrence, and local recurrence. RESULTS: The cohort included 1702 patients treated with curative intent for OSCC according to standardized national guidelines. The 5-year OS was superior in oral tongue to retromolar trigone as well as in both oral tongue and floor-of-mouth (FOM) compared to tumors involving multiple locations. The 3-year RFS in oral tongue and FOM was superior to tumors involving multiple locations, and in FOM compared to retromolar trigone. The 3-year L-RFS in oral tongue and FOM was higher than gingiva, retromolar trigone and tumors involving multiple locations. Adjusting for relevant covariables using oral tongue as reference, tumors involving multiple locations was the only category presenting higher risk for locoregional recurrence, while risk of local recurrence was higher in gingiva, retromolar trigone, hard palate and to tumors involving multiple locations. The study found no difference in risk of death between subsites. CONCLUSION: The study found differences in survival outcomes between subsites. After adjusting for covariables, subsite mainly had significant impact on local recurrence, with no distinct pattern of influence on overall death or locoregional recurrence.

Reexploring Problematic Social Media Use and Its Relationship with Adolescent Mental Health. Findings from the "LifeOnSoMe"-Study.

Purpose: Previous approaches used to assess problematic social media use risk inflating prevalence numbers and classifying unproblematic social media use as problematic. The main aim of this study was to take an exploratory view as to how different types of activities, experiences, and motivations on social media are associated with problematic mental health outcomes in adolescents. Patients and Methods: This study is based on a cross-sectional survey of 2023 adolescents (mean age 17.4 years (SD 0.9), 44.4% males) from the year 2020. Exploratory graph analysis and exploratory factor analysis were performed on 28 pre-selected items assessing adolescents' use of social media, to identify underlying potentially problematic factors associated with social media use. Sets of gender-adjusted multiple linear regression analyses were performed to assess the degree to which social media factors predicted depression, anxiety, well-being, and time spent on social media. Results: Three factors were identified: 1) "subjective overuse", 2) "social obligations", and 3) "source of concern". All three factors showed significant positive associations with mental health problems. The factor "source of concern", which identifies feelings of being overwhelmed and concerned over social media use, had the strongest association to mental health problems and simultaneously the weakest association to time spent on social media. Conclusion: Three identified factors measuring problematic social media use showed positive associations with mental health problems. This lends support to the notion that problematic social media use is a multidimensional phenomenon and demonstrates the need to move beyond addiction criteria when assessing problematic social media use.

Commonly reported negative experiences on social media are associated with poor mental health and well-being among adolescents: results from the "LifeOnSoMe"-study.

Introduction: Cyberbullying has been extensively studied and is associated with adverse mental health outcomes in adolescents. However, adolescents may also experience a range of other negative experiences, such as name-calling, threats, exclusion, and unwanted attention or contact from others. Few studies have investigated how adolescents' mental health is affected by these relatively common and less severe types of negative experiences on social media (SOME). To assess the association between mental health outcomes and two aspects of negative experiences on SOME; unwanted attention and negative acts and exclusion. Methods: This study is based on a survey conducted in 2020/21 consisting of 3,253 Norwegian adolescents (56% female, Mage = 17 years). Eight statements about negative experiences on SOME were asked and combined into two composite measures: "Unwanted attention from others" and "Negative acts and exclusion." Dependent variables in regression models were symptoms of anxiety, symptoms of depression, and mental well-being. Covariates in all models included age, gender, subjective socioeconomic status, and amount of SOME-use. Results: Both "negative acts and exclusion" and "unwanted attention from others" on SOME were consistently positively associated with self-reported symptoms of depression and anxiety, and negatively associated with mental well-being in both crude and adjusted analysis. Discussion: The results are indicative of an important relationship between experiencing negative events on SOME, even presumably less severe events, and worse mental health and well-being. Future research should extricate the potential causal relationship between negative experiences on SOME and mental health, as well as exploring potential precipitating and intermediating factors.

Transplantation of fecal filtrate to neonatal pigs reduces post-weaning diarrhea: A pilot study.

Post-weaning diarrhea (PWD) remains a major source of mortality and morbidity in swine production. Transplantation of bacteria-free filtrate of feces (fecal filtrate transplant, FFT) has shown gut protective effects in neonatal pigs, and early postnatal establishment of the gut microbiome is suggested to determine later stability and robustness of the gut. We, therefore, hypothesized that early postnatal transplantation of bacteria-free feces would have a protective effect against PWD. Using fecal filtrates derived from healthy lactating sows, we compared oral administration of fecal filtrate transplantation (FFT, n = 20) and saline (CON, n = 18) in newborn piglets. We assessed growth, diarrhea prevalence, blood parameters, organ measurements, morphology, and gut brush border enzymes and analyzed luminal bacterial composition using 16S rRNA gene amplicon sequencing. The two groups showed similar average daily gain (ADG) during the suckling period, whereas in the post-weaning period, a negative ADG was observed in both groups. While diarrhea was largely absent in both groups before weaning, there was a lower diarrhea prevalence on days 27 (p = 2.07*10-9), 28 (p = 0.04), and 35 (p = 0.04) in the FFT group relative to CON. At weaning on day 27, the FFT group had higher numbers of red blood cells, monocytes, and lymphocytes, while on day 35, i.e., 1 week after weaning, the two groups were similar regarding hematology. The biochemical profile was largely similar between FFT and CON on days 27 and 35, except for a higher level of alanine aminotransferase and a lower level of Mg in the FFT group. Likewise, organ weights relative to body weight were largely similar on day 35, albeit with a lower stomach weight and more colon content in FFT relative to CON. Gut mucosal percentage and mucosal enzyme activity were similar between the two groups on days 27 and 35. Gut bacterial composition was slightly different on day 35 but not on day 27. In conclusion, early postnatal administration of FFT, showed positive clinical effects in post-weaning pigs, albeit with subtle effects on the gut mucosa and microbiome. Prophylactic treatment with FFT may offer a means to reduce morbidity, yet larger studies are required to document effect size.

Relationship between Ketones, Ghrelin, and, Appetite on Isocaloric Diets with Varying Carbohydrate Quality and Amount: Results from a Randomized Controlled Trial in People with Obesity (CARBFUNC).

BACKGROUND: Low-carbohydrate high-fat (LCHF) diets may suppress the increase in appetite otherwise seen after diet-induced fat loss. However, studies of diets without severe energy restriction are lacking, and the effects of carbohydrate quality relative to quantity have not been directly compared. OBJECTIVES: To evaluated short- (3 mo) and long-term (12 mo) changes in fasting plasma concentrations of total ghrelin, ß-hydroxybutyrate (ßHB), and subjective feelings of appetite on 3 isocaloric eating patterns within a moderate caloric range (2000-2500 kcal/d) and with varying carbohydrate quality or quantity. METHODS: We performed a randomized controlled trial of 193 adults with obesity, comparing eating patterns based on "acellular" carbohydrate sources (e.g., flour-based whole-grain products; comparator arm), "cellular" carbohydrate sources (minimally processed foods with intact cellular structures), or LCHF principles. Outcomes were compared by an intention-to-treat analysis using constrained linear mixed modeling. This trial was registered at clinicaltrials.gov as NCT03401970. RESULTS: Of the 193 adults, 118 (61%) and 57 (30%) completed 3 and 12 mo of follow-up. Throughout the intervention, intakes of protein and energy were similar with all 3 eating patterns, with comparable reductions in body weight (5%-7%) and visceral fat volume (12%-17%) after 12 mo. After 3 mo, ghrelin increased significantly with the acellular (mean: 46 pg/mL; 95% CI: 11, 81) and cellular (mean: 54 pg/mL; 95% CI: 21, 88) diets but not with the LCHF diet (mean: 11 pg/mL; 95% CI: -16, 38). Although ßHB increased significantly more with the LCHF diet than with the acellular diet after 3 m (mean: 0.16 mmol/L; 95% CI: 0.09, 0.24), this did not correspond to a significant group difference in ghrelin (unless the 2 high-carbohydrate groups were combined [mean: -39.6 pg/mL; 95% CI: -76, -3.3]). No significant between-group differences were seen in feelings of hunger. CONCLUSIONS: Modestly energy-restricted isocaloric diets differing in carbohydrate cellularity and amount showed no significant differences in fasting total ghrelin or subjective hunger feelings. An increase in ketones with the LCHF diet to 0.3-0.4 mmol/L was insufficient to substantially curb increases in fasting ghrelin during fat loss.

Prognostic Value of Lymph Node Yield, Lymph Node Density, and pN in Oral Cancer.

OBJECTIVES: To investigate thresholds for lymph node yield (LNY), lymph node density (LND), and pN in patients with oral squamous cell carcinoma in relation to previous findings in the literature. STUDY DESIGN: Retrospective register-based study. SETTING: Copenhagen Oral Cavity Squamous Cell Carcinoma database. METHODS: Appropriate thresholds for LNY, LND, and pN were determined by areas under the curve and subsequently subjected to multivariate analysis. Five-year overall survival and 3-year recurrence-free survival were determined by Kaplan-Meier survival curves. RESULTS: In total, 413 patients diagnosed with oral squamous cell carcinoma were included. In the pN0 cohort, no superior/prognostic LNY cutoff values were detected. In the pN+ cohort, areas under the curve determined thresholds of LNY, LND, and pN to be 21 nodes, 5%, and 3 metastases, respectively. The 5-year overall survival was 52% for patients with LNY ≥21 vs 38% for patients with LNY <21 (hazard ratio [HR], 1.49; 95% CI, 1.05-2.11; P < .05), 60% for patients with LND ≤5% vs 38% for patients with LND >6% (HR, 1.63; 95% CI, 1.03-2.57; P < .05), and 43% for patients with pN <3 vs 26% for patients with pN ≥3 (HR, 1.40; 95% CI, 1.04-2.15; P < .05). CONCLUSIONS: Increased nodal yield, decreased LND, and decreasing number of pN were associated with significantly improved survival outcomes. LNY might serve as a prognosticator of survival as well as a surgical quality indicator. LND may have implications as a tool in cancer staging and treatment planning.

Diets differing in carbohydrate cellularity and amount similarly reduced visceral fat in people with obesity - a randomized controlled trial (CARBFUNC).

BACKGROUND & AIMS: Visceral adipose tissue (VAT) volume is associated with common lifestyle diseases. Dietary quality, including food matrix and degree of carbohydrate cellularity, as well as the carbohydrate/fat ratio, may influence VAT volume. We aimed to determine the effects of isocaloric diets differing in either "cellularity", a novel marker of dietary carbohydrate quality, or carbohydrate amount on visceral fat volume and anthropometric measures in adults with obesity. METHODS: In a randomized controlled trial of 193 people with obesity/central adiposity, we compared changes in VAT volume after 6 and 12 months, measured by abdominal computed tomography, on three isocaloric eating patterns based on "acellular" carbohydrate sources (e.g., flour-based whole-grain products; comparator arm), "cellular" carbohydrate sources (minimally processed foods with intact cellular structures such as fruits, potatoes/tubers, and rice), or low-carbohydrate high-fat (LCHF) principles. Outcomes were compared by an intention-to-treat (ITT) analysis using constrained linear mixed-effects modelling (cLMM) providing baseline-adjusted change scores and proper missing data handling without imputation. RESULTS: 78 and 57 participants completed 6 and 12 months, respectively, with similar intakes of energy (females: 1820-2060 kcal, males: 2480-2550 kcal) and protein (16-17 energy percent, E%) throughout the intervention, and only modest reductions in energy from baseline. Reported dietary intakes were 42-44, 41-42, and 11-15 E% carbohydrate and 36-38, 37-38, and 66-70 E% fat in the acellular, cellular and LCHF groups, respectively. There were no significant between-group differences in VAT volume after 6 months (cellular vs. acellular [95% CI]: -55 cm³ [-545, 436]; LCHF vs. acellular [95% CI]: -225 cm³ [-703, 253]) or after 12 months (cellular vs. acellular [95% CI]: -122 cm³ [-757, 514]; LCHF vs. acellular [95% CI]: -317 cm³ [-943, 309]). VAT volume decreased significantly within all groups by 14-18% and 12-17% after 6 and 12 months, respectively. Waist circumference was reduced to a significantly greater degree in the LCHF vs. acellular group at 6 months (LCHF vs. acellular [95% CI]: -2.78 cm [-5.54, -0.017]). CONCLUSIONS: Despite modest energy restriction, the three isocaloric eating patterns, differing in carbohydrate cellularity and amount, decreased visceral fat volume significantly and to a similar clinically relevant degree. CLINICAL TRIALS IDENTIFIER: NCT03401970. https://clinicaltrials.gov/ct2/show/NCT03401970.

Yogurt Benefits Bone Mineralization in Ovariectomized Rats with Concomitant Modulation of the Gut Microbiome.

SCOPE: Evidence supports that gut-modulating foods potentially can suppress bone loss in postmenopausal women. This study aims to investigate the effect of milk calcium-enriched milk, yogurt, and yogurt-inulin combination on the gut-bone association. METHODS AND RESULTS: A 6-week intervention study is conducted in ovariectomized rats. Four pastes containing milk calcium-fortified milk (M-Ca), milk calcium-fortified yogurt (Y-Ca), inulin-fortified Y-Ca (Y-I-Ca), or an isoconcentration of calcium carbonate (Ca-N), and a calcium-deficient paste are provided. M-Ca does not influence bone mineral density and content (BMD and BMC), femur mechanical strength, or femoral microstructure compared to Ca-N, but Y-Ca increases spine BMD. The serum metabolome reveals that Y-Ca modulated glycine-related pathways with reduced glycine, serine, and threonine. No additive effects of yogurt and inulin are found on bone parameters. Correlation analysis shows that increased lactobacilli and reduced Clostridiaceae members in Y-Ca is associated with an increased spine BMD. Increases in Bifidobacterium pseudolongum, Turicibacter, Blautia, and Allobaculum and gut short-chain fatty acids in Y-I-Ca are not reflected in bone parameters. CONCLUSION: Yogurt as calcium vehicle contributes to increased spine BMD concomitant with changes in the gut microbiome and glycine-related pathways, while adding inulin to yogurt does not affect bone mineralization in ovariectomized rats.

Self-forming double-crosslinked hydrogels by the marriage of catechols and enzyme mimetic polymers.

Self-forming double-crosslinked (DC) hydrogels were designed by incorporating enzyme-mimicking metal coordination polymer crosslinks and catechol chemistry. A macromolecular tris-histidine copper complex acted both as part of the hydrogel network and as a catalyst of catechol oxidation to induce a second hydrogel network by covalent crosslinking of catechol functionalized polymers thus giving catalytic control over hydrogel crosslinking.

The impact of tobacco smoking on survival of patients with oral squamous cell carcinoma: a population-based retrospective study.

BACKGROUND: This article aims to evaluate the impact of smoking status, accumulated tobacco exposure (ATE), and smoking cessation on overall- and disease-free survival (OS and DFS) of patients with oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: Patients with primary OSCC treated with curative intent between 2000 and 2019 in Copenhagen were included (n = 1808). Kaplan-Meier curves and multivariable Cox regression analyses were performed to compare the survival of patients with different smoking history. Interactions between ATE and (A) tumor subsite and (B) excessive alcohol consumption (EAC) on the survival were evaluated using multivariable Cox regression analyses with interaction terms. RESULTS: We included 1717 patients with known smoking status (62.8% males, median age: 64 years (IQR: 57-71 years)), who had a 5-year OS of 53.7% (95%CI: 49.8%-57.9%). Based on fully adjusted multivariable Cox regression analyses, significantly elevated hazard ratios (HRs) for OS and DFS were identified for current, but not former smokers, compared to never-smokers. An approximately linear relationship between continuous ATE and survival estimates was identified. ATE analyzed as a categorical variable showed significantly elevated HRs for OS of patients with all categories (060 PYs), however only for DFS of patients with >60 PYs, compared to 0 PYs. Furthermore, an unfavorable long-term prognosis was evident after >3.5 (OS) and >2.5 (DFS) years from diagnosis for patients who continued smoking compared to patients with smoking cessation at diagnosis. The survival estimates of patients with different tumor subsite and alcohol consumption differed with increasing ATE. CONCLUSION: Tobacco smoking (assessed as smoking status and ATE) was associated with inferior survival (OS and DFS) among patients with OSCC. Unfavorable long-term prognosis was significant for patients who continued smoking compared to patients with smoking cessation at diagnosis. The impact of ATE on survival of patients with OSCC may depend on the tumor subsite and/or alcohol consumption.

Meal patterns associated with energy intake in people with obesity.

It is widely assumed that people with obesity have several common eating patterns, including breakfast skipping, eating during the night and high fast-food consumption. However, differences in individual meal and dietary patterns may be crucial to optimising obesity treatment. Therefore, we investigated the inter-individual variation in eating patterns, hypothesising that individuals with obesity show different dietary and meal patterns, and that these associate with self-reported energy intake (rEI) and/or anthropometric measures. Cross-sectional data from 192 participants (aged 20-55 years) with obesity, including 6 d of weighed food records, were analysed. Meal patterns and dietary patterns were derived using exploratory hierarchical cluster analysis and k-means cluster analysis, respectively. Five clear meal patterns were found based on the time-of-day with the highest mean rEI. The daily rEI was highest among 'midnight-eaters' (10 669 (sd 2301) kJ), and significantly (P < 0·05) higher than 'dinner-eaters' (8619 (sd 2301) kJ), 'lunch-eaters' (8703 (sd 2176) kJ) and 'supper-eaters' (8786 (sd 1925) kJ), but not 'regular-eaters' (9749 (sd 2720) kJ). Despite differences of up to 2050 kJ between meal patterns, there were no significant differences in anthropometric measures or physical activity level (PAL). Four dietary patterns were also found with significant differences in intake of specific food groups, but without significant differences in anthropometry, PAL or rEI. Our data highlight meal timing as a determinant of individual energy intake in people with obesity. The study supports the importance of considering a person's specific meal pattern, with possible implications for more person-focused guidelines and targeted advice.

Association of Cardiac Biomarkers With the Kansas City Cardiomyopathy Questionnaire in Patients With Chronic Kidney Disease Without Heart Failure.

Background The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a measure of heart failure (HF) health status. Worse KCCQ scores are common in patients with chronic kidney disease (CKD), even without diagnosed heart failure (HF). Elevations in the cardiac biomarkers GDF-15 (growth differentiation factor-15), galectin-3, sST2 (soluble suppression of tumorigenesis-2), hsTnT (high-sensitivity troponin T), and NT-proBNP (N-terminal pro-B-type natriuretic peptide) likely reflect subclinical HF in CKD. Whether cardiac biomarkers are associated with low KCCQ scores is not known. Methods and Results We studied participants with CKD without HF in the multicenter prospective CRIC (Chronic Renal Insufficiency Cohort) Study. Outcomes included (1) low KCCQ score <75 at year 1 and (2) incident decline in KCCQ score to <75. We used multivariable logistic regression and Cox regression models to evaluate the associations between baseline cardiac biomarkers and cross-sectional and longitudinal KCCQ scores. Among 2873 participants, GDF-15 (adjusted odds ratio 1.42 per SD; 99% CI, 1.19-1.68) and galectin-3 (1.28; 1.12-1.48) were significantly associated with KCCQ scores <75, whereas sST2, hsTnT, and NT-proBNP were not significantly associated with KCCQ scores <75 after multivariable adjustment. Of the 2132 participants with KCCQ ≥75 at year 1, GDF-15 (adjusted hazard ratio, 1.36 per SD; 99% CI, 1.12-1.65), hsTnT (1.20; 1.01-1.44), and NT-proBNP (1.30; 1.08-1.56) were associated with incident decline in KCCQ to <75 after multivariable adjustment, whereas galectin-3 and sST2 did not have significant associations with KCCQ decline. Conclusions Among participants with CKD without clinical HF, GDF-15, galectin-3, NT-proBNP, and hsTnT were associated with low KCCQ either at baseline or during follow-up. Our findings show that elevations in cardiac biomarkers reflect early symptomatic changes in HF health status in CKD patients.

Bioinspired Metal⁻Polyphenol Materials: Self-Healing and Beyond.

The blue mussel incorporates the polyphenolic amino acid l-3,4-dihydroxyphenylalanine (DOPA) to achieve self-healing, pH-responsiveness, and impressive underwater adhesion in the byssus threads that ensure the survival of the animal. This is achieved by a pH-dependent and versatile reaction chemistry of polyphenols, including both physical interactions as well as reversible and irreversible chemical bonding. With a short introduction to the biological background, we here review the latest advances in the development of smart materials based on the metal-chelating capabilities of polyphenols. We focus on new ways of utilizing the polyphenolic properties, including studies on the modifications of the nearby chemical environment (on and near the polyphenolic moiety) and on the incorporation of polyphenols into untraditional materials.

Acne vulgaris severity graded by in vivo reflectance confocal microscopy and optical coherence tomography.

INTRODUCTION: Acne is an inflammatory disease of the pilosebaceous unit, which can be investigated in vivo using reflectance confocal microscopy (RCM) and optical coherence tomography (OCT). OBJECTIVES: By means of RCM and OCT to identify morphological characteristics of acne that may be associated with clinical acne severity. METHODS: Patients with mild to moderate facial acne (n = 14, Investigators Global Assessment scale, IGA 1-3), and healthy participants (n = 7, IGA 0) were included in this explorative study. A total of 108 RCM image blocks and 54 OCT scans (each RCM and OCT image measuring 6 × 6 mm) were captured from lesional-, perilesional, and lesion-free skin areas. Acne lesions, infundibular regions of follicles and inflammation degree were compared in acne patients and healthy participants. RESULTS: Combined use of RCM and OCT demonstrated infundibular morphology, acne lesions, and blood flow. RCM images of perilesional- and lesion-free skin in acne patients revealed follicle infundibula with hyperkeratinized borders and abundant keratin plugs, contrasting skin of healthy participants. Higher acne severity related to increased number of follicles with hyperkeratotic borders (P = 0.04) and keratin plugs (P = 0.006), increased infundibulum diameter (P < 0.001), increased density of inflammatory cells (P < 0.001), and blood flow (P = 0.03). Acne lesion morphology was not associated with acne severity. CONCLUSION: Combined use of RCM and OCT elucidated distinctive follicle infundibulum characteristics and inflammation degree that were associated with acne severity. Future trials may apply imaging techniques to support clinical acne grading, and monitor treatment efficacy. Lasers Surg. Med. 51:104-113, 2019. © 2018 Wiley Periodicals, Inc.

Influence of Metal Ions on the Melting Temperature, Modulus, and Gelation Time of Gelatin Gels: Specific Ion Effects on Hydrogel Properties.

The impact of ions on hydrogel strength is not well understood, in particular with regards to specific ion effects for cations. Herein, we find that divalent and monovalent cations in most cases reduce the modulus and melting temperature while increasing the gelation time of gelatin hydrogels. This behavior is in contrast to the well-known stiffening effect of trivalent metals. The melting temperature, the logarithm of the gelation time, and the logarithm of the amplitude of the complex modulus were found to follow a power law dependence on ionic strength: kI x. The power law exponent, x, was found to be universal within the groups of monovalent and divalent cations. The prefactor k depended linearly on the ionic radius, which was used as a proxy for ion polarizability. The slope of this linear dependence was different for monovalent and divalent cations.

Mussel-Inspired Self-Healing Double-Cross-Linked Hydrogels by Controlled Combination of Metal Coordination and Covalent Cross-Linking.

Mussel-inspired hydrogels held together by reversible catecholato-metal coordination bonds have recently drawn great attention owing to their attractive self-healing, viscoelastic and adhesive properties together with their pH-responsive nature. A major challenge in these systems is to orchestrate the degree of catechol oxidation that occurs under alkaline conditions in air and has a great impact on the aforementioned properties because it introduces irreversible covalent cross-links to the system, which stiffens the hydrogels but consume catechols needed for self-healing. Herein, we present a catechol-based hydrogel design that allows for the degree of oxidative covalent cross-linking to be controlled. Double cross-linked hydrogels with tunable stiffness are constructed by adding the oxidizable catechol analogue, tannic acid, to an oxidation-resistant hydrogel construct held together by coordination of the dihydroxy functionality of 1-(2'-carboxyethyl)-2-methyl-3-hydroxy-4-pyridinone to trivalent metal ions. By varying the amount of tannic acid, the hydrogel stiffness can be customized to a given application while retaining the self-healing capabilities of the hydrogel's coordination chemical component.

Bioinspired Ultratough Hydrogel with Fast Recovery, Self-Healing, Injectability and Cytocompatibility.

Inspired by the mussel byssus adhesiveness, a highly hydrated polymeric structure is designed to combine, for the first time, a set of interesting features for load-bearing purposes. These characteristics include: i) a compressive strength and stiffness in the MPa range, ii) toughness and the ability to recover it upon successive cyclic loading, iii) the ability to quickly self-heal upon rupture, iv) the possibility of administration through minimally invasive techniques, such as by injection, v) the swelling ratio being adjusted to space-filling applications, and vi) cytocompatibility. Owing to these characteristics and the mild conditions employed, the encapsulation of very unstable and sensitive cargoes is possible, highlighting their potential to researchers in the biomedical field for the repair of load-bearing soft tissues, or to be used as an encapsulation platform for a variety of biological applications such as disease models for drug screening and therapies in a more realistic mechanical environment. Moreover, given the simplicity of this methodology and the enhanced mechanical performance, this strategy can be expanded to applications in other fields, such as agriculture and electronics. As such, it is anticipated that the proposed strategy will constitute a new, versatile, and cost-effective tool to produce engineered polymeric structures for both science and technology.